The focus of this proposal is to study the influence of functionally distinct subsets of CD4 T lymphocytes on B cell and macrophage activation and function. Previous studies in this laboratory have shown that CD4 T cells can be subdivided into two functionally distinct subsets whose functional capabilities correlate with the unique panel of cytokines each releases upon activation. Given that their functions appear quite distinct with one subset playing a primary role in B cell activation, IgE secretion, mast cell and eosinophil amplification and the other subset mediating delayed type hypersensitivity responses, cytolysis and macrophage activation, it would appear that each subset would contribute to immunity against microorganisms which are either extracellular or intracellular microorganisms, respectively. The present studies will address the following issues. 1) What is the function of cloned and uncloned subsets of CD4 in B cell and macrophage activation in vivo and in vitro; 2) What is the lineage relationship between the two subsets of T cells in terms of their effector function and phenotype if individual subsets are used to reconstitute B or scid mice; and 3) Are experimental models exhibiting deficiency in a particular type of immunity examples of deficiencies in the effector functions provided by a subset of CD4 T cell.